Spontaneous Emulsification Method Research Articles

Nanoemulsion Formulation And Activity Test Of Essential Oil Basil Leaves (Ocimum basilicum L.) Against Salmonella typhi


 Essential oil of basil (Ocimum basilicum L.) leaves with a concentration of 2.5% can be estimated to have a diameter of inhibition zone with an average value of 8.67 ± 0.58 mm. Essential oils have volatile characteristics, and are easily oxidized so that they can affect their activities as antibacterial. To increase stability, essential oils of basil leaves need to be packaged in a special delivery system.
 Nanoemulsion is made by spontaneous emulsification method. Nanoemulsion was further tested for physical characteristics including droplet size, polydispersity index, zeta potential and nanoemulsion morphology using a Transmission Electron Microscope (TEM). The preparation was then tested for its activity against Salmonella thypi. The method used is the Kirby-Bauer disk diffusion method.
 From the test of physical characteristics obtained the average particle size of 10.6 nm, polydispersity index 0.03 and zeta potential -36.4. The results of the observation using TEM form the particles produced are spherical. Antibacterial test results were shown by the formation of inhibition zones of basil leaf essential oil (9.3 mm), positive control (6.6 mm), negative control (7.5 mm), nanoemulsion of basil leaf essential oil (8.3 mm), Virgin Coconut Oil (7 mm). Based on the results of statistical analysis it was found that there were no significant differences in treatment between groups.

Preparation, Characterization and Evaluation of Curcumin Nanodispersions Using Three Different Methods – Novel Subcritical Water Conditions, Spontaneous Emulsification and Solvent Displacement

Abstract Curcumin as a lipophilic bioactive compound can be incorporated into water-based formulations when it turns into curcumin nanodispersions. In fact, nanodispersion systems, increase curcumin bioavailability, solubility and stability, and furthermore increase curcumin uses in aqueous food and pharmaceutical formulations. Present study focuses on the preparation of curcumin nanodispersions under subcritical water conditions (temperature of 120 °C and pressure of 1.5 bar for 2 h) and using selected another two different methods namely, spontaneous emulsification and solvent displacement. Lecithin as carrier oil, Tween 80 as emulsifier and polyethylene glycol as co-surfactant, with a ratio of 1:8:1, were used in all the preparation techniques. Obtained results indicated that curcumin nanodispersions with smallest mean particle size (70 nm), polydispersity index (0.57), curcumin loss (5.5%) and turbidity (0.04 Nephelometric Turbidity Unit), and maximum loading ability (0.189 g/L), loading efficiency (94.5%) and conductivity (0.157 mS/cm) were obtained under subcritical water conditions. The results also exhibited that the prepared spherical curcumin nanoparticles in the water by this technique had desirable physical stability as their mean zeta potential value was (−12.6 mV). It also observed that, as compared to spontaneous emulsification and solvent displacement methods, the prepared curcumin nanodispersions via subcritical water method had highest anti-oxidant and antibacterial activities.

Enhancing analgesic and anti-inflammatory effects of capsaicin when loaded into olive oil nanoemulsion: An in vivo study

Topical preparations of capsaicin, the major pungent ingredient of hot pepper, are being used for management of pain and inflammatory disorders. Purpose of this study was to use nanoemulsion as an effective topical drug carrier for in vivo delivery of capsaicin. An oil-in-water nanoemulsion containing capsaicin was prepared by spontaneous emulsification method. Optimized formulation showed a median droplet diameter (d50) of 13–14 nm and was stable for more than 8 months in room and harsh temperature (i.e. 4 and 45 °C). The nanoemulsion was then formulated into topical cream and gel to compare its efficacy and safety profiles with conventional cream of capsaicin. Skin irritation study showed that topical application of capsaicin nanoemulsion was safe and no sign of edema and erythema was observed. The preparation significantly decreased inflammation of rats paw edema compared to the commercial cream and control group, especially in 2nd and 3rd hours of the test. Also, pretreated rats with capsaicin nanoemulsion gel showed very good resistance to the pain caused by heat stimulus. In total, the selected nanoemulsion showed great potential as carrier for topical delivery of capsaicin for improving its analgesic and anti-inflammatory effects. It was also found that the topical gel outperforms the topical cream as dosage form for the nanoemulsion.

Brinzolamide–loaded nanoemulsions: ex vivo transcorneal permeation, cell viability and ocular irritation tests

The aim of this study was to investigate the corneal penetration of brinzolamide (BZ) nanoemulsions (NEs) and evaluate their in vitro and ex vivo irritancy potential. Twelve BZ NEs were prepared by the spontaneous emulsification method and ex vivo permeability studies were conducted using excised bovine corneas fixed onto Franz diffusion cells. To confirm the safety of the formulations for ophthalmic use, preparations were examined for potential ocular irritancy using a cell viability assay on retinal cells, the Hen's Egg Test-Chorio-Allantoic Membrane (HET-CAM) and the bovine corneal opacity-permeability (BCOP) test. Seven BZ NEs exhibited superior penetration across isolated bovine cornea compared to the marketed BZ suspension. The half maximal inhibitory concentration (IC50) values of various surfactants and oils determined using the sulforhodamine B cell viability assay on retinal cells showed that Transcutol P, Cremophor RH40 and Triacetin were the least toxic excipients and may be safely used in the eye at various concentrations. HET-CAM and BCOP tests revealed that NE6B and NE4C did not result in any irritation and were thus considered safe for ocular use. Our finding suggests that optimized NEs can be a safe and effective vehicle for ocular delivery of BZ.

Novel Drug Delivery Approach via Self-Microemulsifying Drug Delivery System for Enhancing Oral Bioavailability of Asenapine Maleate: Optimization, Characterization, Cell Uptake, and In Vivo Pharmacokinetic Studies.

Asenapine maleate (AM)-loaded self-microemulsifying drug delivery system (AM-SMEDDS) was prepared to increase its oral bioavailability. AM-SMEDDS was developed using Capryol 90, Cremophor EL, and Transcutol HP as oil, surfactant, and cosurfactant, respectively, by spontaneous emulsification method. Pseudoternary diagram showed maximum region at 3:1 ratio of Cremophor EL/Transcutol HP. The AM-SMEDDS showed globule size and zeta potential of 21.1 ± 1.2nm and - 19.3 ± 1.8mV, respectively. Globules were found to be of spherical shape and uniformly distributed by transmission electron microscopy. In vitro drug release study showed 99.2 ± 3.3% of drug release at the end of 8h in phosphate buffer pH 6.8. Ex vivo drug release study showed only 15% of drug diffusion through stomach and ~ 85% drug was diffused through intestinal membrane. Confocal and flow cytometry study showed that cellular uptake of coumarin-6 loaded SMEDDS was significantly enhanced by Caco-2 cells as that of coumarin-6 solution. The relative bioavailability of AM-SMEDDS was found to be 23.53 times greater than AM suspension. Intestinal lymphatic transport study using Cycloheximide(CHX) showed that the AUCtotal of AM-SMEDDS reduced about 35.67% compared with that without the treatment ofCHX indicating involvement of lymphatic system in intestinal absorption of AM-loaded SMEDDS. These findings demonstrated the potential of SMEDDS for oral bioavailability improvement of AM via lymphatic uptake. Graphical Abstract.

Solubility and Dissolution Improvement of Carbamazepine by Various Methods

This work was aimed to improve solubility and dissolution rate of carbamazepine (CBZ), an antiepileptic, BCS class II drug by using different solubility enhancement techniques. Self-nanoemulsifying drug delivery system (SNEDDS) and solid dispersions of CBZ was attempted by spontaneous emulsification method and fusion method, respectively. The solubility studies of pure CBZ was performed in different oils, surfactants and co-surfactants. Very small amount of CBZ (20 mg) could be incorporated in SNEDDS, however the solid dispersion of CBZ using Soluplus® was successfully prepared with the required dose. The solid dispersion was characterized and evaluated for saturation solubility, in vitro dissolution studies, solid state characterization such as fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction studies (XRD). Based on the results, it can be concluded that the due to increased solubility and the dissolution, the bioavailability of CBZ could be improved by preparing solid dispersion

The innovative fabrication and applications of carvacrol nanoemulsions, carboxymethyl chitosan microgels and their composite films.

Carvacrol (CA) was firstly made into physically stable nanoemulsions using an innovative spontaneous emulsification method with carvacrol itself as oil phase without introducing other carrier oils. Self-crosslinking carboxymethyl chitosan (CMC) microgels via intermolecular hydrogen bonds were then fabricated using a simple solvent exchange method with ethanol as poor solvent. The CMC microgels obtained were rapidly deposited on the surface of tin foil using an electrospray technique to produce the CMC films. The stability of the films in water was further intensified by using Ca2+ as cross-linking agent. Also, the carvacrol nanoemulsions (CA-NEs) were loaded into the CMC films by utilizing swelling property of CMC microgels in aqueous solution. The results showed that the CA-NEs@CMC composite films possess satisfactory antioxidant activity, good antibacterial activity against S. aureus and E. coli, and excellent ability to extend the shelf life of wheat bread. We believe that the present strategies to prepare CA-NEs, CMC microgels and their composite films also apply to other types of essential oils and polymers, and the CA-NEs@CMC composite film is an excellent candidate for the active packaging.

Evaluation of cytotoxicity, genotoxicity and ecotoxicity of nanoemulsions containing Mancozeb and Eugenol

Mancozeb is a fungicide widely used in agriculture, mostly against the pathogen Glomerella cingulata responsible for the rot of ripe grape, but presents high toxicity. Strategies are sought to reduce the toxicity of this fungicide and alternative treatments are welcome. An alternative could be the use of clove oil, which has Eugenol as its major compound, and has antifungal potential against G. cingulata, however, Eugenol is susceptible to degradation processes which may compromise its efficacy. The nanoencapsulation of Mancozeb and Eugenol is a possible strategy to overcome the limitations of toxicity, solubility and instability of these compounds. Therefore, the objective of this study is to develop nanoemulsions containing Mancozeb (0.1 mg/mL) and Eugenol (33 mg/mL), isolated or associated, and evaluate the safety of these formulations through cytotoxicity, genotoxicity and ecotoxicity tests. Nanoemulsions were developed by the spontaneous emulsification method, cytotoxicity and genotoxicity were evaluated in healthy human cells through MTT, Dichlorofluorescein diacetate and Picogreen tests, and ecotoxicity assessment was carried out using the chronic toxicity test in springtails. After preparation, the physicochemical characterization of the nanoemulsions were performed which presented mean particle size between 200 and 300 nm, polydispersity index less than 0.3, negative zeta potential and acid pH. The nanoencapsulation was able to avoid the reduction of the cell viability caused by Mancozeb, while Eugenol was shown to be safe for cell use in both free and nanostructured forms, however the association of the two active compounds showed toxicity in the higher doses of Mancozeb. In the ecotoxicity tests, both free Mancozeb and Eugenol forms presented high toxic potential for soil, whereas the nanoencapsulation of these compounds did not cause a reduction in number of springtails. Therefore, from the tests performed, it was possible to observe that nanoencapsulation of Mancozeb and Eugenol is a safe alternative for the application of these compounds mainly in agriculture.

Nanoemulsions containing mancozeb and eugenol: development, characterization, and antifungal activity against Glomerella cingulata

The grape culture is quite affected by fungi. Among them is Glomerella cingulata, whose control is carried by synthetic fungicides such as mancozeb, which can cause damage to human and environmental health. An alternative is the use of natural fungicides, such as eugenol. It has already proven antifungal activity but has instability problems. In this context, nanoencapsulation would be a possibility to minimize the mancozeb toxicity and the eugenol instability. In this study, nanoemulsions containing eugenol and mancozeb, isolated and in association, were prepared by the spontaneous emulsification method. Afterwards, the antifungal activity, through the macrodilution technique in broth and the physicochemical stability of these formulations were evaluated. The nanoemulsions presented adequate nanometric characteristics with diameter between 180 and 210 nm, polydispersity index less than 0.3, negative zeta potential and acid pH. Besides good physicochemical stability. The compounds when nanoencapsulated presented an antifungal activity against G. cingulata with efficacy 103 and 3 times better for mancozeb and eugenol, respectively, compared to its free form. The study demonstrates the viability of obtaining nanoemulsions containing mancozeb and/or eugenol with antifungal activity against of G. cingulata, having these an innovative character for the treatment of vine-growing pests.

FORMULATION AND EVALUATION OF RED PALM OLEIN NANOEMULSION

Objective: The objective of this study is to formulate and evaluate the red palm olein (RPO) nanoemulsion using spontaneous emulsification method.Methods: Nanoemulsion formulated by spontaneous emulsification method using the comparison of surfactant (tween 80) and cosurfactant (sorbitol) concentration with the variation of RPO concentration. Evaluation of the stability of the nanoemulsion preparation includes centrifugation test, viscosity, pH, organoleptic observation (odor, color, clarity, and phase separation), and particle size measurement during 12 weeks storage at room temperature.Result: The results showed that all nanoemulsion preparations were transparent yellow, characteristic odor, type weights 1.0166–1.0641 g/ml, and stable for 12 weeks storage at room temperature. The smallest particle size was produced by the nanoemulsion preparation in a formula of the concentration of 5%, which was 67, 64 nm.Conclusion: RPO can be formulated as a nanoemulsion by spontaneous emulsification method. RPO with a 5% concentration is very stable for 12 weeks storage.

Astaxanthin-alpha tocopherol nanoemulsion formulation by emulsification methods: Investigation on anticancer, wound healing, and antibacterial effects

Emulsion-based delivery systems have been fabricated and developed to increase the bioavailability of astaxanthin and alpha-tocopherol as active compounds for various biomedical applications. Astaxanthin-alpha tocopherol nanoemulsion (ATNE) is well known for its potential 6.-6.30 effect. The current study investigated ATNE by spontaneous (SENE) and ultrasonication emulsification (USNE) methods to optimally fabricate oil/water nanoemulsion characterized for biomedical applications. The two methods were compared by using a response surface method of 3-level Box-Behnken design (BBD) with significant factors. Transmission electron microscopy (TEM) confirmed spherical-shaped nanoemulsion from SENE and USNE methods and dynamic light scattering (DLS) proved the good stability of the fabricated nanoemulsion. Cytotoxicity studies on three different cancer cells confirmed that the nanoemulsion at higher concentrations was more toxic than one at lower concentrations by accompanying a significant decrease in the cellular viability after 24 and 48 h of exposure. The wound-healing potential using scratch assay evidenced faster healing effect of the nanoemulsion. Both minimal inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC) methods confirmed significant antibacterial activity to disrupt the integrity of the bacterial cell membrane. The current results suggested that ATNE act as effectively targeted drug delivery vehicles in the future for cancer treatment applications due to its significant results of anticancer, wound healing, and antimicrobial effects.

Physical Characterization and Dissolution Study of Pentagamavunon-0 Loaded Self Nano-Emulsifying Drug Delivery System

The recent work focuses on the physical characterization and dissolution study of PGV-0 loaded self-nanoemulsifying drug delivery system (SNEDDS). The PGV-0 SNEDDS was prepared by spontaneous emulsification method using oleic acid, tween 20:labrasol (1:1) and polyethylene glycol 400. The zeta potential of the PGV-0 SNEDDS was -34.4 ± 7.66 mv. The nanoemulsion of PGV-0 SNEDDS was thermodynamically stable with forming droplet oil containing PGV-0 in it and spherical. The dissolution result showed that the PGV-0 SNEDDS was able to increase the dissolution significantly (p <0.05) compared with PGV-0 powder of 44.13% in AGF medium and 30.37% in AIF medium. It is concluded that SNEDDS PGV-0 was able to increase the PGV-0 aqueous solubility.

Localized In Situ Nanoemulgel Drug Delivery System of Quercetin for Periodontitis: Development and Computational Simulations.

This study was aimed at formulating a bioabsorbable, controlled-release, nanoemulgel of Quercetin, a potent antimicrobial and anti-inflammatory agent for the treatment of periodontitis that could improve its solubility and bioavailability. Screening of components was carried out based on the solubility studies. Nanoemulsion containing cinnamon oil as the oil phase, tween 80 and Carbitol® as the surfactant-cosurfactant mixture (Smix) and water as the aqueous phase containing 125 µg/200 µL of Quercetin was prepared by using spontaneous emulsification method. Nanoemulgel was prepared using 23% w/v poloxamer 407 as gel base. Comprehensive evaluation of the formulated nanoemulgel was carried out, and the optimized formulation was studied for drug release using Franz vertical diffusion cells. The formulated nanoemulgelexhibited a remarkable release of 92.4% of Quercetin at the end of 6 h, as compared to that of pure Quercetin-loaded gel (<3% release). The viscosity of the prepared nanoemulgel was found to be 30,647 ± 0.32 cPs at 37 °C. Also, molecular dynamics (MD) simulation was utilized to understand the gelation process and role of each component in the formulation. The present study revealed that the developed nanoemulgel of Quercetin could be a potential delivery system for clinical testing in periodontitis.

Exploring the anti-quorum sensing activity of a d-limonene nanoemulsion for Escherichia coli O157:H7.

In this study, a d-limonene nanoemulsion was developed by using a spontaneous emulsification method and its potential to inhibit the quorum sensing (QS)-regulated properties of Escherichia coli O157:H7 (E. coli) were revealed. The results in this study showed that d-limonene nanoemulsion inhibited E. coli biofilm formation through the suppression of curli and extracellular polymeric substance (EPS) production without inhibiting cell growth, and decreased swimming and swarming ability. Further analyses showed that d-limonene nanoemulsion interfered with auto-inducer 2 (AI-2) communication and repressed the expression of curli related genes and AI-2 importer genes in E. coli. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1979-1986, 2018.

FORMULATION DEVELOPMENT AND CHARACTERIZATION OF SNAKEHEAD FISH POWDER IN ORAL DOUBLE EMULSION

Objective: Snakehead fish has been scientifically proven to increase levels of albumin and boost the immune system so that the formulation development is required. The objective of this study was to formulate and characterize snakehead fish powder (SFP) in the form of the oral double emulsion.Methods: The manufacture of snakehead fish powder used the conventional method with dry heating at 50 °C. Characterization of SFP utilized proximate analysis method per 3 g of SFP. The double emulsion preparation was carried out by mixing 30% of the primary emulsion (w/o) into 70% of the secondary emulsion (w) to form the w/o/w emulsion. This preparation was prepared in 4 formulas having variations in Tween 80 concentrations at the secondary emulsions of 0.7%, 3.5%, 7.0% and 10.5% w/v, respectively using the spontaneous emulsification method. After that, all formulations were doing some tests, i.e. organoleptic test, pH, viscosity, flow types, globular diameter test and stability tests.Results: The results of proximate analysis every 3 g of SFP have obtained the contents of protein, 16.89%, lipid 24.52%, water 1.73% and ash 1.05%. Based on the optimization of the formula, the preparation of F4 with the content of Tween 80 at 10.5% secondary emulsion is the best formula due to slow phase separation, pH 7, unchanged organoleptic properties, large internal and external globular diameter (6.35 μm and 8.9 μm), as well as having a high viscosity value (1569.84 p) which correspond to pseudo plastic flow.Conclusion: The novelty of SFP can be developed as double emulsion orally based on the results of characterization and evaluation of double emulsion.

Nanoemulsion of atovaquone as a promising approach for treatment of acute and chronic toxoplasmosis

Treatment of toxoplasmosis is necessary in congenital form and immunocompromised patients. Atovaquone is a powerful suppressor of protozoan parasites with a broad-spectrum activity, but an extremely low water solubility and bioavailability. In this study, nanoemulsion of this drug was prepared with grape seed oil using spontaneous emulsification method to increase bioavailability and efficacy of atovaquone for treatment of toxoplasmosis. In vitro activity of atovaquone nanoemulsion against T. gondii, RH and Tehran strains, was assessed in HeLa cell culture. For in vivo assessment, BALB/c mice were infected with RH and Tehran strains and then treated with nanoemulsion of atovaquone, compared to that treated with free atovaquone. Concentration of atovaquone nanoemulsion showed in vitro anti-parasitic effects in both strains of T. gondii. Furthermore, oral administration of atovaquone nanoemulsion increased oral bioavailability, tissue distribution and mice survival time and reduced parasitemia and number and size of the brain cysts. Decrease of cyst numbers was verified by down regulation of BAG1 using real-time polymerase chain reaction (real-time PCR) assay. Effective therapeutic activity of atovaquone at a reduced dose is the major achievement of this study.

Development and evaluation of sea buckthorn (Hippophae rhamnoides L.) seed oil nanoemulsion gel for wound healing

Background: Sea buckthorn (SBT) seed oil is reported to have significant wound-healing activity. However, the oil presents with problems such as poor skin permeation and retention in the deeper layers of skin, as well as leakage, dripping, and spreading during application. These issues can be overcome by formulating nanoemulsion (NE) gel of SBT seed oil. Objective: The present study involves the development of SBT seed oil NE gels for wound healing. Materials and Methods: The NE formulations were prepared by the spontaneous emulsification method. Based on the results of pseudoternary phase diagrams, different NE formulations were prepared using SBT seed oil, surfactant/cosurfactant, and water. The selected NE formulation NEA1 was used to prepare two NE gels containing 0.5% w/w (NG1) and 1% w/w (NG2) of carbopol 940. Results: The optimized formulation NEA1 was selected on the basis of stability and conductivity studies. The NG2 NE gel was selected as the final formulation on the basis of viscosity, spreadability, extrudability, and texture analysis. This optimized NG2 formulation was further evaluated for in vivo wound-healing activity and ex vivo skin penetration studies. A significant improvement was found in NG2-treated group of animals in comparison with SBT seed oil-treated animals w.r.t wound contraction, hydroxyproline, hexosamine content, breaking strength, tensile strength, and epithelialization time of the wound. The optimized formulation also showed improved antibacterial and antifungal activity. Conclusion: The formulated NE gel of SBT seed oil showed better wound-healing, antibacterial, and antifungal activity in comparison to pure SBT seed oil. Abbreviations used: CPCSEA: Committee for the Purpose of Control and Supervision of Experiments on Animals; DMSO: Dimethyl sulfoxide; FITC: Fluorescein isothiocyanate; FAME: Methyl esters formation of fatty acids; GC: Gas chromatography; IAEC: Institutional Animal Ethics Committee; MIC: Minimum inhibitory concentration; MHA: Mueller-Hinton agar media; MHB: Mueller-Hinton broth; MDS: Mean droplet size; NIPER: National Institute of Pharmaceutical Education and Research; NEs: Nanoemulsions; KOH: Potassium hydroxide; PDI: Polydispersity index; RPMI-1640: Roswell Park Memorial Institute-1640 medium; STZ: Streptozotocin; SBT: Sea buckthorn; Smix: surfactant/cosurfactant; TEA: Triethanolamine; TEM: Transmission electron microscopy; YPD: Yeast extract-peptone-dextrose.

Development of a Novel Spontaneous Emulsification Method for Peptide Delivery Using Porous Silica Particles.

A new emulsification technique using porous silica particles was studied as a facile and instantaneous formation method for thermodynamically unstable emulsions. In this study, oil encapsulated in silica particles was released instantly upon the addition of a phosphate buffer, forming an oil-in-water (O/W) emulsion. Emulsion formation was inhibited or promoted using lipophilic or hydrophilic surfactant additives, respectively. We concluded that this phenomenon is affected by the wettability of the soybean oil on the silica surface, which is controlled by the surfactant. We prepared submicron size emulsions in a simple method involving the addition of the silica particles to an aqueous solution. This spontaneous emulsification technique could be applied to the formation of solid-in-oil-in-water (S/O/W) emulsions for oral delivery of hydrophilic peptide medicine.

Magnetic Nanoemulsions: Comparison between Nanoemulsions Formed by Ultrasonication and by Spontaneous Emulsification.

Nanoemulsions are particularly suitable as a platform in the development of delivery systems. The type of nanoemulsion with a higher stability will offer an advantage in the preparation of a delivery system for lipophilic drugs. Nanoemulsions can be fabricated by different processing methods, which are usually categorized as either high- or low-energy methods. In this study, a comparison between two methods of preparing magnetic oil-in-water (O/W) nanoemulsions is described. The nanoemulsions were formed by sonication (the high-energy method) or by spontaneous emulsification (the low-energy method). In both cases, the oil phase was olive oil, and a phospholipid and a pegylated phospholipid were used as emulsifiers. To favor the comparison, the amounts of the components were the same in both kinds of nanoemulsions. Moreover, nanoemulsions were loaded with hydrophobic superparamagnetic nanoparticles and indomethacin. In vitro, releases studies indicated a short drug burst period followed by a prolonged phase of dissolutive drug release. The Korsmeyer-Peppas model can fit the associated kinetics. The results showed that such nanoemulsions are suitable as a platform in the development of delivering systems for lipophilic drugs. The long-term stability was also examined at different temperatures, as well as the interaction with plasma proteins. Nanoemulsion obtained by the low-energy method showed a great stability at 4 °C and at ambient temperature. Its size and polydispersity did not change over more than two months. The spontaneous emulsification method therefore has great potential for forming nanoemulsion-based delivery systems.

Formulation Development and Evaluation of the Therapeutic Efficacy of Brinzolamide Containing Nanoemulsions.

Brinzolamide (BZ) is an intraocular pressure reducing agent with low bioavailability. The purpose of the present study was to overcome this issue by development of BZ containing nanoemulsions (NEs) as an ocular drug delivery system with desirable therapeutic efficacy. Brinzolamide NEs were prepared by the spontaneous emulsification method. Based on initial release studies, twelve formulations with the slowest release characteristics were subjected to further physicochemical investigations such as particle size, polydispersity index, pH, refractive index, osmolality and viscosity. The therapeutic efficacy of these formulations was assessed by measuring the intraocular pressure after instillation of the prepared NEs in normotensive albino rabbit eyes. Nanoemulsions with suitable physicochemical properties exhibited high formulation stability under different conditions. more over biological evaluations indicated that using lower drug concentrations in NE formulations (0.4%) had a similar or even better pharmacodynamic effect compared to the commercial suspension with a higher drug concentration (1%). Our findings suggest that NEs could be effectively used as carriers for enhancing the bioavailability of topically applied ophthalmic drugs.